Assay for detecting, measuring and monitoring the activities and concentrations of proteins and methods of use thereof

    公开(公告)号:US06746850B2

    公开(公告)日:2004-06-08

    申请号:US09848370

    申请日:2001-05-04

    IPC分类号: C12Q146

    摘要: An assay for detecting, measuring, or monitoring the activity or concentration of at least two proteins that have similar or overlapping properties is disclosed. The assay comprises first determining the sensitivity coefficients of the substrates for each of the proteins in which the concentrations are to be determined. This method may be used for detecting, measuring, or monitoring the activity and concentration of AChE, BChE, or both in a test sample which test sample may be whole and unprocessed blood or tissue. Also disclosed are methods of using the assay to detect a subject's exposure to an agent which affects cholinesterase, determine the efficacy or progress of a treatment, determine the amount of protection provided against exposure to an agent which affects cholinesterase, or both, screen a subject for having a drug sensitivity or a particular disease, detect a change in red blood cell count of a subject, determine whether a candidate compound affects cholinesterase. Also disclosed are devices and kits for detecting, measuring, or monitoring the activities and concentrations of AChE, BChE, or both.

    Liposomes containing novel targeting and/or fusogenic peptides, preparations containing them and therapeutic use thereof
    4.
    发明授权
    Liposomes containing novel targeting and/or fusogenic peptides, preparations containing them and therapeutic use thereof 失效
    含有新靶向和/或融合肽的脂质体,含有它们的制剂及其治疗用途

    公开(公告)号:US07741431B2

    公开(公告)日:2010-06-22

    申请号:US11339404

    申请日:2006-01-25

    摘要: A novel targeting peptide from the C-terminal of endothelin and/or a novel fusogenic peptide from hemagglutinin are optionally conjugated to the carboxy group of 1,2-dioleoyl-sn-glycero-3-succinate and incorporated into liposomes for therapeutic treatment. The novel targeting peptide directs liposomes to lung cells, and, therefore, is useful for delivering liposomes encapsulating cholinesterase genes, particularly, the human serum butyryl cholinesterase (Hu BChE) gene, as a treatment against nerve agents. It is emphasized that this abstract is provided to comply with the rules requiring an abstract which will allow a searcher or other reader quickly to ascertain the subject matter of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the appended issued claims. 37 CFR §1.72(b).

    摘要翻译: 任选地,将来自血管凝血酶的C端的新型靶向肽和/或来自血凝素的新的融合肽缀合到1,2-二油酰-sn-甘油基-3-琥珀酸酯的羧基上并且并入脂质体中进行治疗。 新型靶向肽将脂质体引导至肺细胞,因此可用于递送包封胆碱酯酶基因的脂质体,特别是人血清丁酰胆碱酯酶(Hu BChE)基因作为神经药物的治疗。 要强调的是,该摘要被提供以符合要求抽象的规则,这将允许搜索者或其他读者快速地确定技术公开的主题。 提交它的理解是,它不会用于解释或限制所附权利要求的范围或含义。 37 CFR§1.72(b)。

    Previns as specific inhibitors and therapeutic agents for botulinum toxin B and tetanus neurotoxins
    7.
    发明授权
    Previns as specific inhibitors and therapeutic agents for botulinum toxin B and tetanus neurotoxins 失效
    前列腺素作为肉毒杆菌毒素B和破​​伤风神经毒素的特异性抑制剂和治疗剂

    公开(公告)号:US07235521B1

    公开(公告)日:2007-06-26

    申请号:US09979101

    申请日:2000-05-15

    IPC分类号: A61K38/00

    摘要: The compounds of the invention are generally described by the formula (1): B1Z*2B3Z*4X*5Q6F7X8X9X10X11, (2): B1X2X3X4X5Q6F7X8X9X10X11, or (3): B1X2B3X4Z5Q6F7Z8X9X10X11 and the salts, esters, amides, and acyl forms thereof. Each position represented by a letter indicates a single amino acid residue: B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. As described below, one or more of the peptide linkages between the amino acid residues may be replaced by a peptide linkage mimic. These compounds may be used as molecular building blocks to create compounds that are optimized for inhibiting the protease activity of Botulinum B and tetanus toxins.

    摘要翻译: 本发明的化合物通常由式(1)描述:B 1 Z * 2 B 3 Z * 4 < 5×6×6×6××××××××××××××××××××××××××××××××××××××××××< (2):B 1 X 2 X 3 X 2 X 2 X 3 5 5 5 或(3):B 1 X 2 B 3 3 5 X 5 5 5 它们的盐,酯,酰胺和酰基形式。 由字母表示的每个位置表示单个氨基酸残基:B是碱性或极性/大氨基酸或其修饰形式; X是小或疏水性氨基酸或其修饰形式; X *是小或极/大氨基酸或其修饰形式; Z是极性/大或疏水性氨基酸或其修饰形式; Z *是脯氨酸或极性/大或疏水性氨基酸或其修饰形式。 如下所述,氨基酸残基之间的一个或多个肽键可以被肽键模拟物代替。 这些化合物可用作分子结构单元以产生针对抑制肉毒杆菌B和破伤风毒素的蛋白酶活性而优化的化合物。

    Previns as specific inhibitors and therapeutic agents for Botulinum toxin B and Tetanus neurotoxins
    9.
    发明授权
    Previns as specific inhibitors and therapeutic agents for Botulinum toxin B and Tetanus neurotoxins 失效
    前列腺素作为肉毒杆菌毒素B和破​​伤丹神经毒素的特异性抑制剂和治疗剂

    公开(公告)号:US06573244B1

    公开(公告)日:2003-06-03

    申请号:US09570022

    申请日:2000-05-12

    IPC分类号: A61K3800

    摘要: The compounds of the invention are generally described by the formula: B1Z*2B3Z*4X*5Q6F7X8X9X10X11  (1), B1X2X3X4X5Q6F7X8X9X10X11  (2), or B1X2B3X4Z5Q6F7Z*8X9X10X11  (3) and the salts, esters, amides, and acyl forms thereof. Each position represented by a letter indicates a single amino acid residue: B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. As described below, one or more of the peptide linkages between the amino acid residues may be replaced by a peptide linkage mimic. These compounds may be used as molecular building blocks to create compounds that are optimized for inhibiting the protease activity of Botulinum B and tetanus toxins.

    摘要翻译: 本发明的化合物通常用下式描述:或其盐,酯,酰胺及其酰基形式。 由字母表示的每个位置表示单个氨基酸残基:B是碱性或极性/大氨基酸或其修饰形式; X是小或疏水性氨基酸或其修饰形式; X *是小或极/大氨基酸或其修饰形式; Z是极性/大或疏水性氨基酸或其修饰形式; Z *是脯氨酸或极性/大或疏水性氨基酸或其修饰形式。 如下所述,氨基酸残基之间的一个或多个肽键可以被肽键模拟物代替。这些化合物可以用作分子结构单元以产生针对抑制肉毒杆菌B和破伤风的蛋白酶活性而优化的化合物 毒素

    Buforin I as a specific inhibitor and therapeutic agent for botulinum toxin B and tetanus neurotoxins
    10.
    发明授权
    Buforin I as a specific inhibitor and therapeutic agent for botulinum toxin B and tetanus neurotoxins 失效
    Buforin I作为特异性抑制剂和肉毒杆菌毒素B和破​​伤风神经毒素的治疗剂

    公开(公告)号:US06713444B1

    公开(公告)日:2004-03-30

    申请号:US09570023

    申请日:2000-05-12

    IPC分类号: A61K3800

    CPC分类号: C07K14/8146 A61K38/00

    摘要: The compounds of the invention are generally described by the formula: X1X2B3X4B5X*6X7X8 B9X10B11X12B13X14 B15X16B17X*18X*19B20 X21X22X23Q24F25Z*26X27 X28B29X30B31B32X33X34 B35B36X37Z38Z39  (1) and the salts, esters, amides, and acyl forms thereof. Up to 15 amino acids may be truncated from the N-terminus and up to 6 amino acids may be truncated from the C-terminus. Each position represented by a letter indicates a single amino acid residue wherein B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. These compounds may be used to inhibit the protease activity of Botulinum B and tetanus toxins.

    摘要翻译: 本发明的化合物通常用下式描述:及其盐,酯,酰胺及其酰基形式。 可以从N末端截断至多15个氨基酸,并且可以从C末端截断至多6个氨基酸。 由字母表示的每个位置表示单个氨基酸残基,其中B是碱性或极性/大氨基酸或其修饰形式; X是小或疏水性氨基酸或其修饰形式; X *是小或极/大氨基酸或其修饰形式; Z是极性/大或疏水性氨基酸或其修饰形式; Z *是脯氨酸或极性/大或疏水性氨基酸或其修饰形式。 这些化合物可用于抑制肉毒杆菌B和破伤风毒素的蛋白酶活性。